title: Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients.
abstract: High-level expression of mitotic arrest defective protein 2 (MAD2), a central component of the spindle assembly checkpoint, has been observed in a variety of human malignancies. Aim of the present study was to observe the expression of MAD2 in human non-small-cell lung cancer (NSCLC) and explore its clinicopathologic significance and evaluate MAD2 expression as a prognostic marker. MAD2 transcript was found to be overexpressed in the great majority of lung cancers by semi-quantitative RT-PCR. A total of 358 NSCLCs were analyzed immunohistochemically on tissue microarrays. High-level MAD2 expression was observed in 26.3% (94 of 358 cases), and correlated with male sex (P=0.0002), tumor progression (pT status) (P=0.0009), visceral or parietal pleural invasion (P=0.0151), non-adenocarcinoma, histological classification (P<0.0001), and smoking history (P=0.0022), but not with patient age or lymph node metastasis (pN status). Patients with tumors displaying high-level MAD2 expression showed significantly shorter survival (P<0.0001, log-rank test). Similarly, gender, pT status, pN status, pleural invasion, histological classification, and smoking history were significant prognostic markers in univariate Cox survival analysis. Importantly, high-level MAD2 expression was also identified as an independent prognostic factor by multivariate analysis (P=0.0076). These results provide additional prognostic information for surgical treatment of NSCLC.
authors.affiliation: Department of Thoracic Surgery, Sapporo Minami-Sanjo Hospital, S3W6 Chuo-ku, Sapporo 060-0063, Japan. katotatu7@msn.com
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kato
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
authors.forename: Masato
authors.initials: M
authors.lastname: Aragaki
authors.forename: Keidai
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
authors.forename: Mitsuhito
authors.initials: M
authors.lastname: Kaji
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D064246:Mad2 Proteins; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D040081:Protein Array Analysis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D012907:Smoking; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins